tbuckley/cabot-search huggingface dataset:
Comparison of systematic inflammatory prognostic scores in patients with advanced pancreatic adenocarcinoma.
Authors: Lucy Xiaolu Ma, Osvaldo Espin-Garcia, Yifan Wang, Michael J Allen, Gun Ho Jang, Amy Zhang, Anna Dodd, Stephanie Ramotar, Shawn Hutchinson, Mustapha Tehfe, Ravi Ramjeesingh, James Joseph Biagi, Julie Wilson, Faiyaz Notta, Sandra Fischer, George Zogopoulos, Steven Gallinger, Robert C. Grant, Jennifer J. Knox, Grainne M. O'Kane
Journal: Journal of Clinical Oncology (2022)

4149 Background: Systemic inflammatory scores have been developed as tools to aid clinicians in prognostication and patient (pt) selection for clinical trials. We compared the accuracy of five prognostic scores to predict overall survival (OS) in pts with advanced pancreatic adenocarcinoma (PDAC). Methods: Pts with advanced PDAC enrolled on the COMPASS trial (NCT02750657) from 2015 to 2020 were included. All pts had biopsies for whole genome and RNA sequencing prior to standard first-line chemotherapy in the advanced setting. Prognostic risk was calculated using: neutrophil-to-lymphocyte ratio (NLR; &gt;5 = high), platelet-to-lymphocyte ratio (PLR; &gt; 150 = high), Prognostic Nutritional Index (PNI = albumin + 5 x lymphocytes. PNI &lt; 45 = high risk), Gustave Roussy Immune Score (GRIm-S; NLR&gt;6 = 1 point, albumin &lt;35 = 1 point, LDH &gt; upper limit of normal [ULN] = 1 point. GRIm-S ≥2 = high risk), and Memorial Sloan Kettering Prognostic Score (MPS; NLR &gt;4 and albumin &lt; 40 = high risk). OS was estimated using the Kaplan-Meier method and compared between risk groups (high vs. not-high) for each scoring system using the log-rank test. Cox proportional hazards models were used to analyze the association between each prognostic score and OS, adjusting for baseline clinical and genomic factors. Results: In total, 263 pts with advanced PDAC cancer were included, with median follow up of 32.9 (95% CI 15.9-64.2) months. Median OS in the intention to treat population was 9.3 months (95% CI 8-10.2). PLR and PNI were not prognostic. High risk NLR (N=85, 32%), GRIm-S (N=47, 18%) and MPS (N=46, 17%) identified pts with poor prognosis. The GRIm-S and MPS were most significant: median OS in high vs low risk pts 6.4 vs. 10 months p&lt;0.001 (GRIm-S) and 6.3 vs. 10 months p=0.002 (MPS). On multivariable analyses, high risk NLR, GRIm-Score and MPS were each associated with poor OS after adjusting for baseline clinical and genomic factors (Table). For all models, ECOG ≥1 (N=165, 63%); the basal-like Moffitt RNA subtype (N=49, 20% vs 80% classical) and low HRDetect scores (N=31, 13%) were significantly associated with poor OS. However these scores did not associate with RNA based classifiers or HRD scores and can therefore provide additional prognostic information. Conclusions: Both the GRIm-S and MPS are highly prognostic in PDAC and are scores easily used in the clinical setting and may help in clinical trial selection. Genotypic correlates are being explored.[Table: see text]
Impact of the COVID-19 pandemic on colorectal cancer (CRC) care: Data from 22 German cancer centers (CC) and the Institute of Pathology, Ruhr-University Bochum - the AIO (Working Group for Internal Oncology of the German Cancer Society) CancerCOVID Consortium - AIO-YMO/KRK 520/ass.
Authors: Celine Lugnier, Sarah Foerster, Anna-Lena Kraeft, Inke Sabine Feder, Jens Christmann, Eleni Kourti, Oliver Overheu, Sabine Sommerlatte, Waldemar Uhl, Martin Schoenlein, Vivian Rosery, Christoph Biermann, Lothar Müller, Olaf Schoffer, Jochen Schmitt, Dominik Paul Modest, Volker Heinemann, Jan Schildmann, Anke C. Reinacher-Schick, Andrea Tannapfel
Journal: Journal of Clinical Oncology (2022)

3626 Background: CRC still is one of the leading causes of cancer related death though prognosis has improved through guideline based management. The COVID-19 pandemic lead to re-allocation of resources subordinating all sections of care for CRC patients. We present data on changes of CRC care during the pandemic from 22 German AIO CC and our high volume Institute of Pathology (pathology). Methods: Data was collected retrospectively comparing the months (mo) of the first wave (fw) (4-6/2020) and second wave (sw) (11-12/2020) of the pandemic with corresponding periods (cp) in 2019 focusing on the number of precancerous (ICD-O/0+2) and malignant (ICD-O/3+6) colorectal lesions (CRL) diagnosed by our pathology, the number/stage of primary diagnoses (PD) and the number of surgeries (surg) at AIO CC. There, quality criteria of CRC care were also assessed (number of PD discussed within a multidisciplinary tumor board (tb), received social service (soc)/ psychological (psy) counseling or recruited into a clinical trial). Statistical analysis was performed using students t-test for paired data. Results: Numbers of CRL detected upon histology (row 1-3), number of cases, surg and quality criteria from AIO CC (row 4-9) are displayed in the table. We saw a dip in diagnosed CRL and number of surg (p=0.007) only during fw, whereas PD dipped significantly in both waves. A significant reduction in diagnosis of stage III CRC was detected for 2019 vs. 2020 (p=0.001), not for other stages. Quality criteria showed a significant reduction in clinical trial inclusion, a small dip in soc/psy counseling and persistently high tb presentation. Conclusions: We detected a significant decrease of premalignant lesions and primary cancers during the first year of the pandemic which may impact cancer mortality in the future. Certified German CC provided CRC care with significant reduction in clinical trial inclusion only, suggesting high stability of established certified cancer care infrastructure.[Table: see text]
Race, age, and sex differences on the influence of obesity on colorectal cancer (CRC) sidedness and mortality: A national cross-sectional study.
Authors: Mark Bilinyi Ulanja, Bryce D. Beutler, Daniel Antwi-Amoabeng, Ganiyu A. Rahman, Reginald N. Ulanja, Tariq Mabrouk, Olatunji B. Alese
Journal: Journal of Clinical Oncology (2022)

3527 Background: CRC sidedness has recently been recognized as a significant prognostic factor for survival; left-sided colorectal cancer (LCRC) is associated with superior outcomes as compared to right-sided colon cancer (rCC). Although obesity has long been recognized as a risk factor for CRC, the influence of obesity on CRC sidedness remains to be elucidated. To evaluate the effect of obesity on CRC sidedness and determine how race, age, and sex affect mortality among individuals with obesity and CRC. Methods: A survey-weighted analysis was conducted using data obtained from the National Inpatient Sample (NIS) between 2016 and 2019. Results: Of the 24,549 patient discharges included in the cohort with a diagnosis of CRC and a reported body mass index (BMI), 52.6% were LCRC and 47.5% were rCC. The race distribution was 67.7% White, 17.6% Black, 10.0% Hispanic, and 4.8% Other (American Indian, Asian, Pacific Islander, or Alaskan Native). Overweight and obese individuals were more likely to have rCC as compared to normal weight patient discharges [adjusted OR (aOR) = 1.28; 95% CI:1.17 – 1.39 and aOR = 1.45; 95% CI:1.37 –1.54, respectively). In addition, among the obese population, Blacks were more likely to have rCC as compared to Whites (aOR = 1.23; 95% CI: 1.09 – 1.38). Normal weight, overweight, and obese individuals in the “Other” race category had increased odds of death as compared to all other races (aOR=1.18; 95% CI:1.13-1.22; aOR=1.09 95% CI: 0.99-1.19; and aOR=1.19; 95% CI: 1.13-1.25, respectively). Overweight and obese patient discharges over the age of 65 years were more likely than their younger counterparts to present with rCC. As compared to males, females had a higher likelihood of presenting with rCC irrespective of weight, but lower mortality across all weight categories (Table). Conclusions: Obesity is associated with an increased risk of rCC. Racial disparities in CC sidedness and outcomes are particularly pronounced among the overweight and obese population. Investigation into causes of these disparities may help improve outcomes among all individuals with CRC. [Table: see text]
Challenges faced by female oncologists in sub-Saharan Africa.
Authors: Miriam Claire Mutebi, Naa Adorkor Aryeetey, Laura M. Carson, Sitna Ali Mwanzi, Dorothy Chilambe Lombe, Edom Seife Woldetsadik, Susan Citonje Msadabwe, Nwamaka Lasebikan, Zainab Mohamed, Doreen Ramogola-Masire, Haimanot Kasahun Alemu, Matthew Jalink, Reshma Jagsi, Verna D. Vanderpuye, Nazik Hammad
Journal: Journal of Clinical Oncology (2022)

11001 Background: Recent articles by ASCO and ESMO have identified challenges facing female oncologists in western contexts. The challenges female oncologists face in sub-Saharan Africa (SSA) have yet to be explored. This study was launched by the AORTIC Education and Training Committee to determine the most common and substantial challenges faced by female oncologists in SSA and identify potential solutions. Methods: A diverse panel of 32 female oncologists from 20 countries in SSA was recruited through professional and personal networks. Following an initial meeting to review terminology, a modified three-round Delphi process took place. Participants iteratively reviewed a list of previously identified challenges facing women in oncology in SSA and identified new challenges. The survey was conducted via REDCap, a secure-web-based software platform. Participants reflected on personal experiences or those of colleagues, and were asked to indicate their agreement with each listed challenge, as well as propose solutions. Descriptive statistics identified the most common challenges. Following the third survey, a focus group was held to enrich study data. A thematic analysis is being conducted on the focus group transcript to identify key themes, and a subsequent modified Delphi process is being executed to build consensus around potential solutions to identified challenges. Results: Response rates for the 3 modified Delphi rounds were 66%, 66%, and 53%. The challenge with the greatest agreement was, “pressure to maintain a work-family life balance and meet social obligations”. These were felt to be unique to women in SSA due to an extended family network with several responsibilities beyond the nuclear family. The next two top-scored challenges were “lack of female support and networks”, and “micro-aggressions” (Table). Conclusions: Female oncologists in SSA experience many of the challenges that have been previously identified by similar studies in other regions, with different degrees of perceived importance. Some challenges have a different lived experience for female oncologists in SSA. The second part of this study will include thematic analysis of the recent focus group and explore potential solutions to mitigate these challenges, which will add insight and potential paths forward to optimizing a diverse workforce in SSA.[Table: see text]
Anlotinib plus radiotherapy-temozolomide for newly diagnosed glioblastoma: A prospective, multicenter phase II study.
Authors: Shuzhen Lai, Yuan yuan Yuan Chen, Peijing Li, Fagui Jiang, Xiaohui Liu, Changjuan Tao, Jing Huang, Yiqiang Tang, Zhigang Liu, Guoping Shen, Chaoming Li, Tieming Xie, Fangxiao Lu, Guihong Liu
Journal: Journal of Clinical Oncology (2022)

e14020 Background: Concurrent radiotherapy and temozolomide (TMZ) followed by adjuvant TMZ (STUPP regimen) is the standard therapy for newly diagnosed glioblastoma after resection, however, the progression-free survival (PFS) was only about 7 months (m) and the overall survival (OS) was less than 17m. This study aims to assess the efficacy and safety of adding anlotinib, a multitarget tyrosine kinase inhibitor, to the STUPP regimen for newly diagnosed glioblastoma. Methods: This was a prospective, sing-arm, multicenter, phase II study (NCT04119674). Eligible patients (pts) were diagnosed with newly diagnosed GBM and had undergone surgery within 6 weeks before enrollment. Previous exposure to other therapies was not permitted. Other key inclusion criteria included 18 to 75 years old, Karnofsky performance status ≥ 60 %, had at least one measurable lesion according to RANO criteria, and adequate bone marrow, hepatic, and renal functions. All pts received radiotherapy (54̃60 Gy administered as 1.8-2.0 Gy fractions, 5 days per week) for 6 weeks, with concurrent oral TMZ (75 mg/m2 QD) and anlotinib (8 mg QD, d1̃d14 per 3 weeks). After a 28-day treatment break, adjuvant therapy was started with six cycles of TMZ (150–200mg/m2, d1–5/4wks) and eight cycles of anlotinib (10 mg QD, d1–14/3wks) ，and followed by anlotinib monotherapy until disease progression or intolerable toxicities. The primary endpoint was progression-free survival (PFS). The adverse events (AEs) were recorded according to CTCAE 5.0. Results: From January 2019 to February 2021, 33 pts (17 males and 16 females) were enrolled from 7 hospitals in China. The median age was 52 (range: 32, 69). At the data cutoff date on January 25th, 2022, all pts had completed the concurrent treatment and 30 pts (90.0%) completed the 6 cycles of adjuvant treatment. The median treatment duration of anlotinib was 16 cycles. At the data cutoff date, 21 patients experienced disease progression and 17 pts were dead. The median PFS was 10.9m (95% CI, 6.6-15.2) and the median OS reached 18.7m (95% CI, 15.0-22.4). The PFS at 1 year was 45.5% and OS at 1 year was 72.7%. No grade 3 or worse AEs were observed during the concurrent phase and anlotinb maintenance phase. Three pts (9.1%) had grade 3 or 4 thrombocytopenia and 1 pts (3.0%) had grade 3 vomiting during the course of adjuvant therapy. Conclusions: This is the first study to explore the feasibility of adding anlotinib to the standard treatment for newly diagnosed GBM. The efficacy was impressive in that the median OS had exceeded 18m and the safety profile was favorable. The positive-controlled study was ongoing. Clinical trial information: NCT04119674.
Patient-reported distress at a cancer center during the COVID-19 pandemic.
Authors: Manan P Shah, Sarah Rosenthal, Mohana Roy, Ali Raza Khaki, Tina Hernandez-Boussard, Kavitha Ramchandran
Journal: Journal of Clinical Oncology (2022)

e18644 Background: Assessments of health-related quality of life (HRQOL) are conducted by health systems to analyze and improve patient-centered care. Numerous studies have shown that the COVID-19 pandemic poses unique stressors for patients with cancer. However, the impact of the pandemic on HRQOL in patients with cancer is unknown. This study investigates change in self-reported global health scores in patients with cancer before and during the COVID-19 pandemic. Methods: In this single-institution retrospective cohort study, patients who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) at a comprehensive cancer center before and during the COVID-19 pandemic were identified. Surveys were analyzed to assess change in the PROMIS global mental health (GMH) and global physical health (GPH) scores at different time periods (pre-COVID: 3/1/5/2019-3/15/2020, surge1: 6/17/2020-9/7/2020, valley1: 9/8/2020-11/16/2020, surge2: 11/17/2020-3/2/2021, and valley2: 3/3/2021-6/15/2021). Results: A total of 29,983 surveys among 7,209 patients were included in the study. Mean GMH scores for patients before the COVID-19 pandemic (50.57) were similar to that during various periods during the pandemic: surge1 (48.82), valley1 (48.93), surge2 (48.68), valley2 (49.19). Mean GPH score was significantly higher pre-COVID (42.46) than during surge1 (36.88), valley1 (36.90), surge2 (37.33) and valley2 (37.14) (Table). During the pandemic, mean GMH (49.00) and GPH (37.37) scores obtained through in-person were similar to mean GMH (48.53) and GPH (36.94) scores obtained through telehealth. Conclusions: In this single institution study, patients with cancer reported stable mental health and deteriorating physical health during the COVID-19 pandemic as indicated by the PROMIS survey. Modality of the survey (in-person versus telehealth) did not affect scores. [Table: see text]
Discovering colorectal cancer biomarkers with individual fragments analysis of cell-free DNA using attention-based deep multi-instance learning.
Authors: Eunsaem Lee, Seungho Shin, Seungtae Park, Seunghyeon Yu, Shin-Sang Jo, Hee Joon Jeon, Na Ri Yoon, Jinho Kim, Donghyun Park, Hyung Ju Hwang
Journal: Journal of Clinical Oncology (2022)

3539 Background: Cell-free DNA(cfDNA) are DNA fragments circulating in blood stream. Among these fragments, there are tumor-derived DNA(ctDNA) fragments which can be a significant biomarker for cancer diagnostics. Recently, there are evidences that reveals methylation patterns of ctDNAs facilitate statistical models to diagnose cancers with plausible accuracy than mutation patterns. Despite of such promising facts, an early detection of cancers with methylation patterns of ctDNAs is still statistically difficult since proportion of ctDNAs to cfDNAs is marginal. As a result, it is difficult to set differential threshold on ctDNA proportion to successfully classify early cancer patients. For such a reason, we develop a high-throughput classifier whose classification resolution is per-fragment unlike per-batch approach in existing models. Methods: Targeted methylation sequencing was performed with DNA extracted from plasma cfDNA of 141 colon adenocarcinoma (COAD) patients and 200 healthy individuals. To extract DNA fragment-level methylation status, we profiled the methylation status using Bismark software and home-built python scripts were used to recover methylation status of DNA fragments. We implement an attention based multi-instance learning model which is permutation-invariant with fragments to analyze the impact of individual fragments on COAD prediction. Our models were trained using k-fold cross-validation and to assess generalization performance. Results: We first trained on local differentially methylated regions (DMRs) that contain 80 to 200 CpG sites using our deep learning model. With a single local region, we achieved a mean sensitivity of 87.2% (mean 95% CI 75.8–93.2%) at 97.7% (mean 95% CI 88.3–99.1%) specificity. By analyzing attention weights, we scored on each fragment according to the model contribution to predicting cancers. To find biomarkers, we added up scores according to methylation of each CpG site. Top 10 high scored CpG sites were validated with tissue sample DNA and almost all of them are overlapped with the 10 CpG sites with the highest statistical differences between cancer and normal tissue in the region. For the global region analysis, we combined local DMRs to confirm collaboration between distant regions and other chromosomes in the colorectal cancer prediction. We achieved a mean sensitivity of 93.4% (95% CI 80.1–98.1%) at 98.3% (95% CI 90.4–99.3%) specificity for the global region prediction. Conclusions: Our study shows a potential of targeted sequencing cell-free DNA as a cancer biomarker. An attention based deep learning model allowed for the analysis of individual fragments and showed the potential for biomarker discovery. The model uses only cell-free DNA and excludes tissue sample DNA, which makes our model less sensitive to the tumor heterogeneity.
Parental informed consent comprehension in childhood cancer clinical trials: Associations with social determinants of health.
Authors: Paula Aristizabal, Shilpa Nataraj, Bianca Perdomo, Elena Martinez, Jesse Nodora, Courtney D Thornburg
Journal: Journal of Clinical Oncology (2022)

6512 Background: Adequate informed consent (IC) comprehension is an ethical right prior to participation in clinical trials. Research investigating IC comprehension and associations with social determinants of health (SDoH) is lacking. We assessed whether SDoH and related contextual factors were associated with parental IC comprehension in therapeutic childhood cancer clinical trials. Methods: We prospectively enrolled parents of children with newly-diagnosed cancer. Univariable and multivariable regression were used to assess whether objective IC comprehension and related domains ( Purpose/Procedures/Randomization, Risks/Benefits, Alternatives, and Voluntariness) were associated with SDoH (ethnicity, marital status, language, education attainment, employment, insurance, socio-economic status, health literacy [HL]) and contextual factors (cancer type, voluntariness, satisfaction with IC). Results: Of 223 parents included, 112 (50%) were Hispanic and 38% of Hispanics were monolingual Spanish-speaking. In adjusted multivariable analyses, limited HL was significantly associated with lower overall IC comprehension (β = -7.22; 95% CI, -10.9 to -3.59; P &lt; 0.001) and lower comprehension of Purpose/Procedures/Randomization (β = -7.53; 95% CI, -11.3 to -3.73; P &lt; 0.001), Risks/Benefits (β = -8.14; 95% CI, -15.5 to -0.772; P = 0.031), and Alternatives (β = -17.0; 95% CI, -30.5 to -3.57; P = 0.013). Preferred Spanish language of written/verbal medical information was significantly associated with lower comprehension of Purpose/Procedures/Randomization (β = -8.50; 95% CI, -15.1 to -1.89; P = 0.012) and Voluntariness (β = -20.1; 95% CI, -34.9 to -5.33; P = 0.008). Lower satisfaction with informed consent (β = 0.988; 95% CI, 0.460 to 1.52; P &lt; 0.001) and single marital status (β = -4.42; 95% CI, -7.81 to -1.02; P = 0.011) were significantly associated with lower IC comprehension. Conclusions: Among parents of children with newly diagnosed cancer who provided consent for their child’s participation in a therapeutic clinical trial, limited HL was consistently associated with lower IC comprehension in all domains analyzed, except for Voluntariness. Spanish language preference for medical information was associated with lower comprehension of two domains; and lower satisfaction was associated with lower overall IC comprehension. These findings suggests that parents with limited HL, limited English-proficiency, and lower satisfaction may not fully comprehend the IC and thereby not truly make informed decisions. Our findings highlight the potential role of language-concordant interventions tailored to the participant’s HL level in order to ultimately improve IC comprehension and contribute to a reduction of disparities in clinical trial participation and promote equitable translation of discoveries and treatments to underserved groups.